Polyurethane-polyethylene delamination resistant tubing with gas barrier properties

ABSTRACT

A tube comprising an inner layer, an outer layer and a barrier layer disposed between the inner layer and the outer layer, wherein the barrier layer is bound to the outer layer by a layer of adhesive disposed between the outer layer and the barrier layer and the barrier layer is bound to the inner layer by a layer of adhesive disposed between the inner layer and the barrier layer, wherein the inner layer comprises a polyethylene, the outer layer comprises a thermoplastic polyurethane and the barrier layer comprises a material that acts as a barrier to gas.

RELATED APPLICATIONS

This application is a divisional of and claims the benefit of priorityto U.S. application Ser. No. 13/586,288 filed Aug. 15, 2012 which iscontinuation-in-part of and claims the benefit of priority of U.S.application Ser. No. 13/354,029 filed Jan. 19, 2012, the disclosures ofwhich are incorporated by reference as if fully set forth herein.

FIELD OF THE INVENTION

The present invention relates to polymeric tubing typically formed by aco-extrusion process, the tubing having multiple layers of the same ordifferent polymeric materials, each layer successively adhered to eachother.

BACKGROUND

Tubing comprised of polymeric material is used in many industrial andcommercial applications including in the medical field. Various FDAcompliant plastics are used, depending upon properties desired and theintended applications. Where the tubing is used to transport fluids forin vivo treatment of human patients, selection of the polymericmaterials can be a factor.

Polyvinyl chloride (PVC) is one of the most widely used plastics. Whilestructurally stable and easily formable into desired shapes, PVC istypically manufactured using plasticizers which can migrate out of thePVC matrix into bodily fluids and has other properties not ideallysuited for medical treatment applications. Likewise, due to the inherentnature of plasticized PVC tubing, there arises the potential absorptionof medicines and other components of aqueous fluids used in medicaltreatments into the sidewall of the PVC tube. Polyurethane ispotentially a substitute for PVC. However, dual layer tubing comprisedof polyurethane and polyethylene suffers from the inability of the twolayers to remain adhered to each other under low to moderate stress,strain or mechanical manipulation conditions as well as the inability tosufficiently impede migration of oxygen through the layers. U.S. Pat.No. 4,627,844 to Schmitt (“Schmitt”), the disclosure of which isincorporated herein by reference as if fully set forth, discloses atri-layer tube which is embodied in a commercial product sold under thetrademark “SUREPATH 151” by the Natvar Division of Tekni-Plex, Inc. Asdisclosed in Schmitt, an outer layer of PVC and an inner fluid-contactlayer of low density polyethylene (LDPE) are co-extruded with anintermediate tie layer of ethylene vinyl acetate copolymer (EVA).However, while Schmitt greatly reduces the possibility for the migrationof additives from the PVC to the fluid and absorption of components fromthe fluid to the PVC tubing by providing a LDPE fluid-contact layer,elimination of the PVC is preferred. Other tubing configurations aredisclosed in U.S. Pat. No. 7,647,949, U.S. Pat. No. 4,211,741 and U.S.Patent Publication No. 2007/0119511, the disclosures of which areincorporated by reference as if fully set forth herein. Where medicaltubing is concerned, preservation of the integrity of reagents containedin fluids being routed through the tubing can be a concern. Similarly,prevention of migration of components out of the fluids through thetubing can be an issue. In such applications, incorporation into thetubing of a layer of material comprised of a gas barrier material can beimplemented for purposes of preventing migration of gases such as oxygeninto the fluid thus preserving oxygen sensitive reagents in the fluid.

SUMMARY OF THE INVENTION

In accordance with the invention there is provided a tube comprising aninner layer, an outer layer and a barrier layer disposed between theinner layer and the outer layer, wherein the barrier layer is bound tothe outer layer by a layer of adhesive disposed between the outer layerand the barrier layer and the barrier layer is bound to the inner layerby a layer of adhesive disposed between the inner layer and the barrierlayer, wherein the inner layer comprises a polyethylene, the outer layercomprises a thermoplastic polyurethane and the barrier layer comprises amaterial that acts as a barrier to gas.

The barrier layer preferably comprises more than about 90% by weight ofan ethylene vinyl alcohol copolymer or a polyamide or blends thereof.

The adhesive typically comprises one or more ethylene acryliccopolymers, more typically one or more anhydride grafted ethyleneacrylate copolymers and preferably one or more anhydride graftedethylene methyl acrylate copolymers.

The inner layer typically comprises more than about 90% by weight of apolyethylene and the outer layer comprises more than about 90% by weightof an aromatic or aliphatic polyether based polyurethane.

The barrier layer typically comprises more than about 90% by weight ofan ethylene vinyl alcohol copolymer or a polyamide or blends thereof andthe adhesive comprises more than about 90% by weight of one or moreethylene acrylic copolymers,

The barrier layer can comprise more than about 90% by weight of anethylene vinyl alcohol copolymer or a polyamide or blends thereof andthe inner layer can comprise more than about 90% by weight of apolyethylene and the outer layer can comprise more than about 90% byweight of an aromatic or aliphatic polyether based polyurethane.

The adhesive can comprise more than about 90% by weight of one or moreethylene acrylic copolymers and the inner layer can comprise more thanabout 90% by weight of a polyethylene and the outer layer can comprisesmore than about 90% by weight of an aromatic or aliphatic polyetherbased polyurethane.

The barrier layer can comprises more than about 90% by weight of anethylene vinyl alcohol copolymer or a polyamide or blends thereof, theadhesive can comprise more than about 90% by weight of one or moreethylene acrylic copolymers, the inner layer can comprises more thanabout 90% by weight of a polyethylene and the outer layer can comprisemore than about 90% by weight of an aromatic or aliphatic polyetherbased polyurethane.

The polyethylene typically comprises one or more of a low densitypolyethylene, a linear low density polyethylene and a high densitypolyethylene and the aromatic polyether based polyurethane can comprisea polytetramethyleneglycol-based polyurethane.

The adhesive can comprise more than about 90% by weight of one or moreethylene acrylic copolymers, the inner layer can comprise more thanabout 90% by weight of low density polyethylene (LDPE), the outer layercan comprise more than about 90% by weight of apolytetramethyleneglycol-based polyurethane and the middle layer cancomprise more than about 90% of a material that acts as a barrier togas.

The adhesive typically comprises more than about 90% by weight of one ormore ethylene acrylic copolymers.

The thickness of the polyurethane outer layer is typically between about0.001 inches (0.0254 mm) and about 0.025 inches (0.635 mm), thethickness of the inner polyethylene layer is typically between about0.001 inches (0.0254 mm) and about 0.025 inches (0.635 mm) and thethickness of the barrier layer is typically between about 0.001 inches(0.0254 mm) and about 0.025 inches (0.635 mm).

The inner and outer layers preferably do not visually delaminate whensubjected to a stress and strain up to the tube's elastic yield point asmeasured in a mechanical tester at a pull rate of about 12 inches perminute at ambient conditions of 72 degrees F. (22° C.) and 50% relativehumidity.

Preferably, the tube does not visually delaminate when submersed inwater at 60° C. for 36 hours.

The tube preferably has a central axial fluid flow passage through whichaqueous fluid is routed, the inner layer having a radially inner wallsurface that contacts the aqueous fluid the outer and inner layersresisting delamination when subjected to a stress and strain up to thetube's elastic yield point as measured in a mechanical tester at a pullrate of about 12 inches per minute at ambient conditions of 72 degreesF. (22° C.) and 50% relative humidity. Such a tube preferably does notvisually delaminate after being submersed in water at 60° C. for 36hours.

In such a tube, the thickness of the adhesive disposed between thebarrier layer and the outer layer is preferably between about 0.001inches (0.0254 mm) and about 0.025 inches (0.635 mm) and the thicknessof the adhesive disposed between the barrier layer and the inner layeris preferably between about 0.001 inches (0.0254 mm) and about 0.025inches (0.635 mm)

In another aspect of the invention there is provided a medical tube fortransport of aqueous fluid comprising:

an inner layer comprising more than about 90% by weight of apolyethylene,an outer layer comprising more than about 90% by weight of a an aromaticpolyether-based polyurethane,a barrier layer disposed between the outer and inner layers comprisingmore than about 90% by weight of a material that acts as a barrier togas, and,an adhesive disposed between the barrier layer and the outer layer anddisposed between the barrier layer and the inner layer, the adhesivecomprising one or more ethylene acrylic copolymers,

In such an embodiment, the inner and outer layers preferably do notvisually delaminate when subjected to a stress and strain up to thetube's elastic yield point as measured in a mechanical tester at a pullrate of about 12 inches per minute at ambient conditions of 72 degreesF. (22° C.) and 50% relative humidity.

In such an embodiment, the tube preferably does not visually delaminateafter being submersed in water at 60° C. for 36 hours.

In such an embodiment, the adhesive comprises one or more anhydridegrafted ethylene acrylate copolymers.

In another aspect of the invention there is provided, a medical tube fortransport of an aqueous fluid comprising:

an inner layer comprised of at least about 90% by weight of apolyethylene.an outer layer comprised of at least about 90% by weight of an aromaticpolyether-based polyurethane,a barrier layer disposed between the outer and inner layers comprisingmore than about 90% by weight of a material that acts as a barrier togas, and,an adhesive disposed between the barrier layer and the outer layer anddisposed between the barrier layer and the inner layer, the adhesivecomprising more than about 90% by weight of one or more ethylene acryliccopolymers,wherein the tubing does not visually delaminate after being submersed inwater at 60° C. for 36 hours.

In another aspect of the invention, there is provided a medical tube fortransport of an aqueous fluid comprising:

an inner layer comprised of at least about 90% by weight of a lowdensity polyethylene,an outer layer comprised of at least about 90% by weight of apolytetramethyleneglycol-based polyurethane,a barrier layer disposed between the outer and inner layers comprisingmore than about 90% by weight of a material that acts as a barrier togas, and,an adhesive disposed between the barrier layer and the outer layer anddisposed between the barrier layer and the inner layer, the adhesivecomprising one or more ethylene acrylic copolymers,wherein the tubing does not visually delaminate when subjected to astress and strain up to the tube's elastic yield point as measured in amechanical tester at a pull rate of about 12 inches per minute atambient conditions of 72 degrees F. (22° C.) and 50% relative humidity,and,wherein the tubing does not visually delaminate after being submersed inwater at 60° C. for 36 hours.

In another aspect of the invention there is provided, a method offorming a medical tube comprising an outer layer, an innermost layer andan intermediate layer disposed between the outer layer and the innermostlayer, the method comprising:

selecting a first polymeric material having a selected structuralstability;

selecting a second polymeric material that is inert to aqueous fluids;

selecting a third polymeric material that acts as a barrier to gas;

selecting a fourth polymeric material that readily bonds and adheres tothe first and second polymeric materials on co-extrusion and cooling ofthe materials;

co-extruding the selected first, second, third and fourth polymericmaterials to form the medical tubing in a configuration that has anouter layer comprising at least about 90% by weight of the firstpolymeric material, an inner layer comprising at least about 90% weightof the second polymeric material, a layer disposed between the inner andouter layers that comprises at least about 90% by weight of the thirdpolymeric material, a layer of the fourth material disposed between theouter layer and the layer of the third polymeric material and a layer ofthe fourth material disposed between the inner layer and the layer ofthe third polymeric material.

In such a method, the first polymeric material is typically selected tobe a polyurethane, the second polymeric material is selected to be apolyethylene, the third polymeric material is selected from the groupconsisting of an ethylene vinyl alcohol copolymer and a polyamide andthe fourth polymeric material is one or more ethylene acryliccopolymers,

In such a method, the first polymeric material is preferably selected tobe a polyurethane, the second polymeric material is selected to be apolyethylene, the third polymeric material is selected from the groupconsisting of an ethylene vinyl alcohol copolymer and a polyamide andthe fourth polymeric material is selected such that the medical tubingdoes not visually delaminate after being submersed in water at 60° C.for 36 hours.

In such a method, the adhesive typically comprises one or more anhydridegrafted ethylene acrylate copolymers.

In another aspect of the invention there is provided, a method ofdelivering an aqueous fluid to a subject comprising;

selecting a tube comprising an inner layer, an outer layer and a barrierlayer disposed between the inner and outer layers, wherein the innerlayer comprises a polyethylene, the outer layer comprises athermoplastic polyurethane and the barrier layer comprises one or moreof an ethylene vinyl alcohol copolymer and a polyamide;wherein the tube has a central fluid flow passage surrounded by thelayers;routing an aqueous fluid through the central fluid flow passage of thetube, and, delivering the aqueous fluid routed through the central fluidflow passage into a blood vessel of the subject.

The step of selecting preferably comprises:

selecting the tube such that a layer of an adhesive is disposed betweenthe outer layer and the barrier layer and between the inner layer andthe barrier layer.

The step of selecting typically comprises:

co-extruding the outer, inner and barrier layers and adhesive layers toform the tube and selecting the adhesive to comprise more than about 90%by weight of one or more ethylene acrylic copolymers.

The adhesive typically comprises one or more anhydride grafted ethyleneacrylate copolymers.

The adhesive can comprise one or more anhydride grafted ethylene methylacrylate copolymers.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings depict one or more embodiments of the invention that areshown by way of examples of the invention wherein:

FIG. 1 is a schematic perspective view of a five-layered tube showingthe outer and middle or intermediate layers broken away in order tobetter illustrate the construction and arrangement of the tubing;

FIG. 2 is a cross-sectional view taken along lines 2-2 of the tube 10shown in FIG. 1.

DETAILED DESCRIPTION

There is shown in FIG. 1 an embodiment of a co-extruded five-layertubing 10 according to the invention which comprises an outer layer 1comprised of at least about 90% by weight of a polyurethane material,typically a polytetramethyleneglycol-based polyurethane one example ofwhich is Lubrizol TPU Pellethane 2363-90AE, an inner fluid-contact layer3 comprised of at least about 90% by weight of a polyethylene material,typically a low density polyethylene, one example of which is WestlakeLDPE EM808AA, an intermediate gas barrier layer 5 comprised of at leastabout 90% by weight of an ethylene vinyl alcohol copolymer (EVOH), apolyamide or a mixture or blend of two or more thereof and bondinglayers 7, 9 comprised of an adhesive material that bonds the barrierlayer 5 to the outer 1 and inner 3 layers. The gas barrier layer 5 actsas a barrier to gases generally such as oxygen, nitrogen, hydrogen,chlorine, nitrous oxide and the like. The adhesive layers 7, 9preferably comprise a material that renders the tubing 10 subsequent toextrusion resistant to delamination where the tubing does not visuallydelaminate after being subjected to submersion in water at 60° C. for 36hours and subsequently mechanically flattened by manual squeezing of thetube from its normal round in cross-sectional condition to a flattenedor oval shape cross-sectional shape or condition. The adhesive materialis most preferably selected to comprise one or more ethylene acryliccopolymers, an example of which is an anhydride grafted ethylene methylacrylate copolymer, a specific example of which is an anhydride graftedethylene methyl acrylate copolymer such as commercially availableWestlake Tymax GA 7001 (Anhydride grafted Ethylene Methyl AcrylateCopolymer).

As shown in FIG. 1 the outer layer of polyurethane 1 has a radiallyinner facing surface S1 that binds and adheres to a radially outerfacing surface S2 of the anhydride modified acrylate adhesive layer 7.The adhesive layer 7 has a radially inner facing surface S3 that bindsto the radially outer facing surface S4 of the barrier layer 5. Thebarrier layer 5 has a radially inner facing surface S5 that binds to theradially outer facing surface S6 of another layer 9 of adhesive. Theadhesive layer 9 has a radially inner facing surface S7 that binds tothe radially outer facing surface S8 of the inner polyethylene layer 3.The intermediate barrier layer 5 adheres to the outer 1 and inner 3layers such that the three layers 1, 3 and 5 remain adhered to layers 7,9 and to each other when the tube 10 is subjected to a stress and strainup to the tube's elastic yield point as measured in a mechanical testerat a pull rate of about 12 inches per minute at ambient conditions of 72degrees F. (22° C.) and 50% relative humidity. Mechanical testers formeasuring such stress and strain are knowing in the art, an example ofwhich is a Lloyd LRSK Plus mechanical tester. Elastic yield point is thehighest point at which one or more of the layers of the tubingpermanently deforms or as otherwise defined in “Introduction to PhysicalPolymer Science, 4^(th) Edition,” L. H. Sperling (author), John Wiley &Sons (publisher), 2006, the disclosure of which is incorporated byreference in its entirety as if fully set forth herein.

The layers 1, 3, 5, 7, 9 of such tubing 10 remain adhered to each othersuch that the layers do not visually delaminate after being subjected tosubmersion in water at 60° C. for 36 hours and subsequently mechanicallyflattened by manual squeezing of the tube from its normal round incross-sectional condition to a flattened or oval shape cross-sectionalshape or condition.

As shown in FIGS. 1 and 2, the layers 1, 3, 5 are formed intostructurally stable walls that surround and enclose a central hollowfluid passage 20 through which an aqueous solution is routed and flowsalong an axial A direction contacting the radially inner facing surfaceS9 of the inner layer 3. The adhesive layers 7, 9 bind and hold thestructural layers, inner 3, intermediate 5 and outer 1 together.

The inner layer 3 provides a radially inner fluid-contact surface S9,the thickness, of the inner layer 3 typically ranging in cross-sectionalthickness T1 of between about 0.001 inches (0.0254 mm) and about 0.025inches (0.635 mm). The intermediate layer 5 typically ranges incross-sectional thickness T3 of between about 0.001 inches (0.0254 mm)and about 0.025 inches (0.635 mm). The outer layer 1 typically ranges incross-sectional thickness T5 of between about 0.001 inches (0.0254 mm)and about 0.025 inches (0.635 mm). The adhesive layers 7, 9 typicallyrange in cross-sectional thickness T2, T4 of between about 0.001 inches(0.0254 mm) and about 0.025 inches (0.635 mm).

The polyethylene material is preferably a branched low-densitypolyethylene (LDPE), such as Westlake EM808, available from WestlakeChemical Corporation. The polyethylene material can be a linear lowdensity polyethylene (LLDPE) such as Dowlex 2035G, available from theDow Chemical Company. The polyethylene material can also be ahigh-density polyethylene (HDPE), such as Chevron 9506 HDPE, Chevron9406 HDPE, and Chevron 9503 HDPE, available from Chevron Corporation.The polyethylene material can be a mixture or blend of two or more ofthe aforementioned polyethylene materials.

The polyurethane elastomer (TPU) is typically the reaction product of apolyol and isocyanate and usually includes a combination of hard andsoft segment domains. An aromatic polyether-based TPU or an aliphaticpolyether-based TPU can be used such as a polytetramethyleneglycol-basedpolyurethane. Such examples of these TPU's include the Pellethane2363-90 AE series available from the Lubrizol Corporation.

The respective thickness of each layer of tubing 10 can be controlled byconventional multi-layer extrusion tooling and equipment and typicallyincludes a die set configured for producing multi-layer tubing such as afive-layer tube as shown in FIG. 1. Such a suitable extrusion apparatusis selected so as to provide a uniform thickness of the layers 1, 3, 5,7, 9 along the substantial entirety of the axial length L of all of thelayers 1, 3, 5, 7, 9.

The polymeric materials of which the layers 1, 3, 5, 7, 9 are comprisedare preferably selected so as to be manually flexible along and aroundthe axis A of the tubing. The polymeric materials are also selected soas to maintain the integrity of the tubing 10 (namely delamination doesnot occur) and its transparency or clarity after being subjected toethylene oxide (EtO) and gamma irradiation sterilization processes.

The foregoing description is intended to illustrate and not limit thescope of the invention, those skilled in the art will realize thatequivalents thereof are contemplated by the description above and thatchanges and modifications may be made thereto without departing from thespirit of the invention, all such equivalents, changes and modificationsfalling within the scope of the claims hereof.

1.-25. (canceled)
 26. Method of forming a medical tube comprising anouter layer, an innermost layer and an intermediate layer disposedbetween the outer layer and the innermost layer, the method comprising:selecting a first polymeric material having a selected structuralstability; selecting a second polymeric material that is inert toaqueous fluids; selecting a third polymeric material that acts as abarrier to gas; selecting a fourth polymeric material that readily bondsand adheres to the first and second polymeric materials on co-extrusionand cooling of the materials; co-extruding the selected first, second,third and fourth polymeric materials to form the medical tubing in aconfiguration that has an outer layer comprising at least about 90% byweight of the first polymeric material, an inner layer comprising atleast about 90% weight of the second polymeric material, a layerdisposed between the inner and outer layers that comprises at leastabout 90% by weight of the third polymeric material, a layer of thefourth material disposed between the outer layer and the layer of thethird polymeric material and a layer of the fourth material disposedbetween the inner layer and the layer of the third polymeric material.27. The method of claim 26 wherein the first polymeric material isselected to be a polyurethane, the second polymeric material is selectedto be a polyethylene, the third polymeric material is selected from thegroup consisting of an ethylene vinyl alcohol copolymer and a polyamideand the fourth polymeric material is one or more ethylene acryliccopolymers.
 28. The method of claim 26 wherein the first polymericmaterial is selected to be a polyurethane, the second polymeric materialis selected to be a polyethylene, the third polymeric material isselected from the group consisting of an ethylene vinyl alcoholcopolymer and a polyamide and the fourth polymeric material is selectedsuch that the medical tubing does not visually delaminate after beingsubmersed in water at 60° C. for 36 hours.
 29. The method of claim 28wherein the fourth polymeric material comprises one or more anhydridegrafted ethylene acrylate copolymers. 30.-34. (canceled)
 35. The methodof claim 29 wherein the fourth polymeric material comprises one or moreanhydride grafted ethylene methyl acrylate copolymers.
 36. The method ofclaim 26 wherein the first polymeric material comprises an aromatic oraliphatic polyether based polyurethane and the second polymeric materialcomprises polyethylene.
 37. The method of claim 36, wherein thepolyethylene comprises one or more of a low density polyethylene, alinear low density polyethylene and a high density polyethylene andwherein the aromatic polyether based polyurethane comprises apolytetramethyleneglycol-based polyurethane.
 38. The method of claim 36,wherein the polyethylene comprises a low density polyethylene (LDPE),and the first polymeric material comprises apolytetramethyleneglycol-based polyurethane.
 39. The method of claim 27,where the thickness of the polyurethane outer layer is between 0.001inches and 0.025 inches, the thickness of the inner polyethylene layeris between 0.001 inches and 0.025 inches and the thickness of thebarrier layer is between 0.001 inches and 0.025 inches.
 40. The methodof claim 26, wherein the inner and outer layers do not visuallydelaminate when subjected to a stress and strain up to the tube'selastic yield point as measured in a mechanical tester at a pull rate ofabout 12 inches per minute at ambient conditions of 72 degrees F. and50% relative humidity.
 41. The method of claim 26, wherein the tube hasa central axial fluid flow passage, the inner layer having a radiallyinner wall surface that defines the passage, the outer and inner layersresisting delamination when subjected to a stress and strain up to thetube's elastic yield point as measured in a mechanical tester at a pullrate of about 12 inches per minute at ambient conditions of 72 degreesF. and 50% relative humidity.
 42. The method of claim 26, wherein thethickness of the layer of the fourth material disposed between thebarrier layer and the outer layer is between 0.0001 inches and 0.025inches and wherein the thickness of the layer of the fourth materialdisposed between the barrier layer and the inner layer is between 0.001inches and 0.025 inches.
 43. The method of claim 26, wherein the tubedoes not visually delaminate when submersed in water at 60° C. for 36hours.